Proteolipids are a class of lipoproteins which are soluble in chloroform-methanol. The proteolipid apoprotein, devoid of complex lipids, retains its solubility in chloroform-methanol but can be converted to a water-soluble form. The brain white matter proteolipid protein is quantitatively the major protein of CNS myelin and we propose to study the immunological properties of proteolipid apoprotein. Circulating antibodies have been obtained in rabbits after a single injection of bovine brain white matter proteolipid apoprotein: conditions have been established for the purification of these antibodies and for their detection by double immunodiffusion. In other experiments animals sensitized to apoprotein adsorbed to polystyrene beads and challenged 6 months later have shown severe hind limb paralysis and the appearance of antibodies not only to apoprotein but also to other myelin constituents. We now propose 1) to follow the humoral and cell-mediated responses of rabbits and Lewis rats to immunological challenge by proteolipid apoprotein. Antibodies to proteolipid, basic protein, cerebrosides and GM1 ganglioside will be measured, 2) to develop a radioimmunoassay for the quantitation of proteolipid apoprotein and anti-apoprotein antibodies, and 3) to apply the radioimmunoassay to the study of CSF and serum from patients with multiple sclerosis and other demyelinating disorders. These studies focus on both the primary and secondary responses of the immune system of experimental animals to challenge by proteolipid protein. The availability of anti-proteolipid antibodies and the development of a radioimmunoassay will provide the basis for fundamental studies on the localization and metabolism of the proteolipid protein and could provide new information for following the course of multiple sclerosis and for its diagnosis.